Introduction Sinonasal inverted papilloma (SNIP) is a rare benign epithelial tumor of the nasal cavity and paranasal sinuses that accounts for 0.4% and 4.7% respectively, of all tumors of this anatomical region. Objective To analyze the outcomes after surgical resection of SNIP and identify the risk factors for recurrence in a Swiss tertiary center. Methods We conducted a retrospective review of all cases of SNIP treated at the Lausanne university hospital between 2005 and 2018. All data available on the patients and tumors were collected for analysis. We studied the recurrence rate and looked for risk factors. Results We included 57 patients with a mean age of 55.5 years. There were 46 primary cases (80.7%) and 11 recurrences (19.3%). Maxillary sinus was the most frequent location (33.3%). Approximately half of the patients (52.6%) presented with a T3 tumor according to the Krouse classification. The mean recurrence rate after surgery was of 17.5% and it was more frequent among the patients in the recurrence group (45.5%) than among the primary cases (10.9%), reaching statistical significance (odds ratio [OR] = 6.8; 95% confidence interval [95%CI]: 1.5-30.8; p = 0.0165). Most patients were treated endoscopically (94.7%). Frontal sinus location, higher Krouse stage, and combined approach seemed to increase the risk of recurrence, but without statistical significance. Conclusion Difficult surgical access, as in the case of tumors located in the frontal sinus, higher stage of the disease, and previously operated cases carry the higher risk of incomplete resection and recurrence.
Le patologie della ghiandola sottomandibolare e sottolinguale sono legate principalmente a fenomeni ostruttivi (litiasi e stenosi dei dotti) e, più raramente, a processi neoplastici. Lo sviluppo delle tecniche endoscopiche (scialoendoscopia), della litotripsia extracorporea e degli approcci combinati ha drasticamente ridotto le indicazioni alla sottomandibolectomia per le patologie ostruttive. Attualmente, le indicazioni alla sottomandibolectomia mediante cervicotomia comprendono principalmente le patologie neoplastiche e i rari casi di fallimento di una gestione più conservativa delle ostruzioni litiasiche. Nonostante l’aumento delle tecniche minimamente invasive, qualsiasi chirurgo ORL deve padroneggiare pienamente le tecniche di accesso chirurgico a cielo aperto alle ghiandole sottomandibolare e sottolinguale.
Las patologías de las glándulas submaxilar y sublingual se relacionan principalmente con fenómenos obstructivos (litiasis y estenosis canaliculares) y, en menos ocasiones, con procesos neoplásicos. El desarrollo de las técnicas endoscópicas (sialoendoscopia), de la litotricia extracorpórea, así como de los accesos combinados ha provocado una disminución drástica de las indicaciones de submandibulectomía en las patologías obstructivas. En la actualidad, las indicaciones para una submandibulectomía por cervicotomía engloban principalmente las patologías neoplásicas y los raros casos de fracaso de un tratamiento más conservador de las obstrucciones litiásicas. A pesar del auge de las técnicas mínimamente invasivas, todos los cirujanos otorrinolaringológicos deben dominar perfectamente las técnicas de acceso quirúrgico a cielo abierto de las glándulas submaxilar y sublingual.
Conclusion: There are several factors that influence the final outcome when treating oral squamous cell carcinoma (OSCC). Invasive front phenomena and more importantly their clinicopathological translation can have a direct impact on survival, and subsequently on the decision for an adjuvant treatment. Objectives: In recent years, the concept of tumor-host interaction has been the subject of substantial efforts in cancer research. Tumoral behavior may be better understood when studying the changes occurring at the tumor-host interface. This study evaluated the influence of several clinicopathological features on the outcome of OSCCs. Methods: The clinical records and pathology specimens of 54 patients with OSCC treated by primary resection were reviewed retrospectively. The pathologic features reviewed were: invasive front grading (IFG), stromal reaction, lymphovascular invasion (LVI), perineural invasion (PNI), margin status, and depth of invasion. Results: High IFGs had a significant relationship with pT status and pN status. High IFGs were strongly correlated with nodal metastases (odds ratio (OR) = 4.77; confidence interaval (CI) = 1.37-16.64). Concerning survival, IFG had a strong impact on disease-free survival in patients treated unimodally, as did the depth of invasion in the same group. Lymphovascular involvement was found to have a negative impact on overall survival in patients treated multimodally.
Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3+ T cells, and relatively high levels of BDCA2+ and FOXP3+ cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3+ T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c+ myeloid dendritic cells, and high numbers of FOXP3+ T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.
Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.
Frequent expression of cancer testis antigens (CTA) has been consistently observed in head and neck squamous cell carcinomas (HNSCC). For instance, in 52 HNSCC patients, MAGE-A3 and -A4 CTA were expressed in over 75% of tumors, regardless of the sites of primary tumors such as oral cavity or hypopharynx. Yet, T-cell responses against these CTA in tumor-bearing patients have not been investigated in detail. In this study, we assessed the naturally acquired T-cell response against MAGE-A3 and -A4 in nonvaccinated HNSCC patients. Autologous antigen-presenting cells pulsed with overlapping peptide pools were used to detect and isolate MAGE-A3 and MAGE-A4 specific CD4+ T cells from healthy donors and seven head and neck cancer patients. CD4+ T-cell clones were characterized by cytokine secretion. We could detect and isolate MAGE-A3 and MAGE-A4 specific CD4+ T cells from 7/7 cancer patients analyzed. Moreover, we identified six previously described and three new epitopes for MAGE-A3. Among them, the MAGE-A3111–125 and MAGE-A3161–175 epitopes were shown to be naturally processed and presented by DC in association with HLA-DP and DR, respectively. All of the detected MAGE-A4 responses were specific for new helper epitopes. These data suggest that naturally acquired CD4+ T-cell responses against CT antigens often occur in vivo in HNSCC cancer patients and provide a rationale for the development of active immunotherapeutic approaches in this type of tumor.
Cancer-testis (CT) antigens comprise families of tumor-associated antigens that are immunogenic in patients with various cancers. Their restricted expression makes them attractive targets for immunotherapy. The aim of this study was to determine the expression of several CT genes and evaluate their prognostic value in head and neck squamous cell carcinoma (HNSCC). The pattern and level of expression of 12 CT genes (MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, MAGE-C2, NY-ESO-1, LAGE-1, SSX-2, SSX-4, BAGE, GAGE-1/2, GAGE-3/4) and the tumor-associated antigen encoding genes PRAME, HERV-K-MEL, and NA-17A were evaluated by RT-PCR in a panel of 57 primary HNSCC. Over 80% of the tumors expressed at least 1 CT gene. Coexpression of three or more genes was detected in 59% of the patients. MAGE-A4 (60%), MAGE-A3 (51%), PRAME (49%) and HERV-K-MEL (42%) were the most frequently expressed genes. Overall, the pattern of expression of CT genes indicated a coordinate regulation; however there was no correlation between expression of MAGE-A3/A4 and BORIS, a gene whose product has been implicated in CT gene activation. The presence of MAGE-A and NY-ESO-1 proteins was verified by immunohistochemistry. Analysis of the correlation between mRNA expression of CT genes with clinico-pathological characteristics and clinical outcome revealed that patients with tumors positive for MAGE-A4 or multiple CT gene expression had a poorer overall survival. Furthermore, MAGE-A4 mRNA positivity was prognostic of poor outcome independent of clinical parameters. These findings indicate that expression of CT genes is associated with a more malignant phenotype and suggest their usefulness as prognostic markers in HNSCC.
Mixed medullary‐follicular thyroid carcinoma denotes a rare and heterogeneous group of tumors displaying morphological and immunophenotypical features of both origins within the same lesion.
To assess the influence of hemoglobin (Hb) levels in locally advanced head and neck cancer (LAHNC) patients treated with surgery and postoperative radiotherapy (PORT).Pre- and postoperative Hb levels were collected in 79 patients treated with surgery followed by accelerated PORT for LAHNC. Median follow-up was 52 months (range 12-95 months).Four-year overall survival (OS) rate was 51%. Neither pre- nor postoperative Hb level (< 120 or 130 g/l in women or men, respectively) influenced the outcome. However, when Hb decrease between pre- and postoperative Hb values was taken into account, 4-year OS was significantly higher in patients with Hb difference less than 38 g/l (quartile value) compared with those with Hb decrease 38 g/l or more (61% versus 16%, P = 0.008).Decrease in Hb level by more than 38 g/l after surgery secondary to blood loss influences the outcome when postoperative RT is indicated.
Background The aim of this study was to assess feasibility and efficacy of weekly concomitant boost accelerated postoperative radiation therapy (PORT) with concomitant chemotherapy (CT) in patients with locally advanced head and neck cancer (LAHNC). Methods and Materials Conformal or intensity-modulated 66-Gy RT was performed in 5.5 weeks in 40 patients. Cisplatin was given at days 1, 22, and 43. Median follow-up was 36 months. Results and Discussion Grade 3 mucositis, dysphagia, and erythema was observed in ten (25%), nine (23%), and six (13%) patients, respectively. Grade 3 or more anemia was observed in two (6%) patients, and leukopenia in five (13%) patients. No grade 3 or 4 thrombocytopenia was observed. Grade 3 nephrotoxicity was observed in one patient (3%). No treatment-related mortality was observed. Grade 2 or more xerostomia and edema were observed in ten (25%) and one (3%) patient, respectively. Locoregional relapse occurred in eight patients, and seven patients developed distant metastases. Median time to locoregional relapse was 6 months. Three-year overall, disease-free survival, and locoregional control rates were 63%, 62%, and 81%, respectively. Multivariate analysis revealed that the only prognostic factor was nodal status. Conclusion Reducing overall treatment time using accelerated PORT/CT by weekly concomitant boost (six fractions per week) combined with concomitant cisplatin CT is easily feasible with acceptable morbidity.